The purpose of this project is to explore the interaction between macrophages and NK cells that leads to NK cell production of IFN-g. The underlying hypothesis of the work is that the functions of NK cells in vivo are controlled by macrophages via the production of interleukin (IL)-15 and IL-12. Specifically, the principal investigator proposes to characterize the regulation of IL-15 production by monocytes, the functional effect of this cytokine on NK cells, and the molecular mechanisms of activation induced by IL-15 in NK cells. The results of these studies aim to provide information on the role of IL-15 in innate immunity and on the interaction between macrophages and NK cells in the initial phases of response to infection or malignant transformation in immunocompromised hosts.